Carboxylic acid Subject

Electron tunnelling tlirough monolayers of long-chain carboxylic acids is one aspect of interest since it was assumed tliat such films could be used as gate electrodes in field-effect transistors or even in devices depending on electron tunnelling [24, 26, 35, 36, 37 and 38]- It was found, however, tliat tlie whole subject depends critically on... 

Carboxylic acids are produced when alkynes are subjected to ozonolysis... 

One of the most sensitive tests of the dependence of chemical reactivity on the size of the reacting molecules is the comparison of the rates of reaction for compounds which are members of a homologous series with different chain lengths. Studies by Flory and others on the rates of esterification and saponification of esters were the first investigations conducted to clarify the dependence of reactivity on molecular size. The rate constants for these reactions are observed to converge quite rapidly to a constant value which is independent of molecular size, after an initial dependence on molecular size for small molecules. The effect is reminiscent of the discussion on the uniqueness of end groups in connection with Example 1.1. In the esterification of carboxylic acids, for example, the rate constants are different for acetic, propionic, and butyric acids, but constant for carboxyUc acids with 4-18 carbon atoms. This observation on nonpolymeric compounds has been generalized to apply to polymerization reactions as well. The latter are subject to several complications which are not involved in the study of simple model compounds, but when these complications are properly considered, the independence of reactivity on molecular size has been repeatedly verified. 

In common with other carboxylic acids, the 3-carboxyl of penicillins can be subjected to a variety of transformations, provided that they can be effected under conditions compatible... 

In the early 1930 s, when the prime research aim was the commercial synthesis of the sex hormones (whose structures had just been elucidated), the principal raw material available was cholesterol extracted from the spinal cord or brain of cattle or from sheep wool grease. This sterol (as its 3-acetate 5,6-dibromide) was subjected to a rather drastic chromic acid oxidation, which produced a variety of acidic, ketonic and hydroxylated products derived mainly by attack on the alkyl side-chain. The principal ketonic material, 3j -hydroxyandrost-5-en-17-one, was obtained in yields of only about 7% another useful ketone, 3 -hydroxypregn-5-en-20-one (pregnenolone) was obtained in much lower yield. The chief acidic product was 3j -hydroxy-androst-5-ene-17j -carboxylic acid. All three of these materials were then further converted by various chemical transformations into steroid hormones and synthetic analogs ... 

Because cyano groups may be hydrolyzed to carboxylic acids (Section 20.19), the Sandmeyer preparation of aryl nitriles is a key step in the conversion of arylarnines to substituted benzoic acids. In the example just cited, the o-rnethylbenzonitrile that was formed was subsequently subjected to acid-catalyzed hydrolysis and gave o-rnethylbenzoic acid in 80-89% yield. 

Chiral oxazolines developed by Albert I. Meyers and coworkers have been employed as activating groups and/or chiral auxiliaries in nucleophilic addition and substitution reactions that lead to the asymmetric construction of carbon-carbon bonds. For example, metalation of chiral oxazoline 1 followed by alkylation and hydrolysis affords enantioenriched carboxylic acid 2. Enantioenriched dihydronaphthalenes are produced via addition of alkyllithium reagents to 1-naphthyloxazoline 3 followed by alkylation of the resulting anion with an alkyl halide to give 4, which is subjected to reductive cleavage of the oxazoline moiety to yield aldehyde 5. Chiral oxazolines have also found numerous applications as ligands in asymmetric catalysis these applications have been recently reviewed, and are not discussed in this chapter. ... 

The Pfitzinger reaction describes the condensation of an o-aminophenylglyoxylic acid 16 (which can be generated in situ from an isatin IS) with 2 results in a quinoline-4-carboxylic acid (17), which is the subject of its own chapter in this book. ... 

In addition, Pfister and coworkers investigated 3-hydroxyflavone-6-carboxylic acids as histamine induced gastric secretion inhibitors. After condensing 3-acetyl-4-hydroxybenzoic acid (45) with a variety of aldehydes 46 to deliver the chalcones 47, these purified chalcones were then subjected to the standard AFO conditions to afford flavonols 48 in 51-80% yield. Subsequent alkylation of 48 with methyl iodide or isopropyl iodide followed by saponification of the corresponding esters gave the target compounds. 

The least squares value for the p constant obtained by this procedure is +6.2 it wiU be obviously subject to change as more meta and epi substituents become available. Only the cata-NO group was excluded from the above plot because it causes a strongly enhanced resonance effect in nucleophilic substitution (Section IV,C, l,a) and an anomalous effect of uncertain origin in the dissociation of carboxylic acids. It can be assumed that the reaction constant for 4-chloro-... 

The constitution of carvestrene has been determined, subject to the limitation above referred to as to the constitution of isocarvestrene, by the masterly synthesis achieved by W. H Perkin, Jr., and his colleagues. The starting-point of this synthesis was t-hydroxy-benzoic acid, which was reduced by sodium and alcohol to cyclohexanol-3-carboxylic acid, of the formula—... 

In addition to those methods already discussed, ketones can also be prepared from certain carboxylic acid derivatives, just as aldehydes can. Among the most useful reactions of this type is that between an acid chloride and a Gilman diorganocopper reagent such as we saw in Section 10.8. We ll discuss this subject in more detail in Section 21.4. 

The ionization of alkyl (E)-arylazo ethers is subject to general acid catalysis when the reaction is carried out in the presence of carboxylic acid buffers (see Scheme 6-3), and the ionization is also subject to steric acceleration in the presence of bulky substituents ortho to the azo ether group (Broxton and Stray, 1980 Broxton and McLeish, 1983 a, and earlier work of Broxton s group). 

The present procedure corresponds to the method7 described earlier for the synthesis of 5-oxo-3,5-seco-4-norcholestane-3-carboxylic acid and is useful for preparing large quantities of the subject keto acid. 

Schemes are available, however, that start from the free carboxylic acid, plus an activator . Dicyclohexylcarbodiimide, DCC, has been extensively employed as a promoter in esterification reactions, and in protein chemistry for peptide bond formation [187]. Although the reagent is toxic, and a stoichiometric concentration or more is necessary, this procedure is very useful, especially when a new derivative is targeted. The reaction usually proceeds at room temperature, is not subject to steric hindrance, and the conditions are mild, so that several types of functional groups can be employed, including acid-sensitive unsaturated acyl groups. In combination with 4-pyrrolidinonepyridine, this reagent has been employed for the preparation of long-chain fatty esters of cellulose from carboxylic acids, as depicted in Fig. 5 [166,185,188] ...

The degradation of alkynes has been the subject of sporadic interest during many years, and the pathway has been clearly delineated. It is quite distinct from those used for alkanes and alkenes, and is a reflection of the enhanced nucleophilic character of the alkyne C C bond. The initial step is hydration of the triple bond followed by ketonization of the initially formed enol. This reaction operates during the degradation of acetylene itself (de Bont and Peck 1980), acetylene carboxylic acids (Yamada and Jakoby 1959), and more complex alkynes (Figure 7.18) (Van den Tweel and de Bont 1985). It is also appropriate to note that the degradation of acetylene by anaerobic bacteria proceeds by the same pathway (Schink 1985b). 

Reversed micelles have also shown to be useful not only in bioconversions, but also in organic synthesis. Shield et al. (1986) have reviewed this subject and brought out its advantages in peptide synthesis, oxidation or reduction of steroids, selective oxidation of isomeric mixtures of aromatics, etc. In the oxidation of aromatic aldehydes to carboxylic acids with enzymes hosted in reverse micelles, the ortho substituted substrates react much more slowly than other isomers. 

Reactants with internal nucleophiles are also subject to cyclization by electrophilic sulfur reagents, a reaction known as sulfenylcyclization.92 As for iodolactonization, unsaturated carboxylic acids give products that result from anti addition.93... 

The subjects of this section are two reactions that do not actually involve carbo-cation intermediates. They do, however, result in carbon to carbon rearrangements that are structurally similar to the pinacol rearrangement. In both reactions cyclic intermediates are formed, at least under some circumstances. In the Favorskii rearrangement, an a-halo ketone rearranges to a carboxylic acid or ester. In the Ramberg-Backlund reaction, an a-halo sulfone gives an alkene. 

The recombinantly expressed nitrilase from Pseudomonas fluorescens EBC 191 (PFNLase) was applied in a study aimed at understanding the selectivity for amide versus acid formation from a series of substituted 2-phenylacetonitriles, including a-methyl, a-chloro, a-hydroxy and a-acetoxy derivatives. Amide formation increased when the a-substituent was electron deficient and was also affected by chirality of the a- stereogenic center for example, 2-chloro-2-phenylacetonitrile afforded 89% amide while mandelonitrile afforded 11% amide from the (R)-enantiomer but 55% amide was formed from the (5)-enantiomer. Relative amounts of amide and carboxylic acid was also subject to pH and temperature effects [87,88]. 

Four macrolides, 11-undecanolide (12-membered,UDL) [85,86], 12-dodeca-nolide (13-membered,DDL) [86,87], 15-pentadecanolide (16-membered, PDL) [85,86,88,89], and 16-hexadecanolide (17-membered, HDL) [90], were subjected to the lipase-catalyzed polymerization. For the polymerization of DDL, lipases CC, PC, PF, and PPL showed the high catalytic activity and the activity order in the bulk polymerization was as follows lipase PC > lipase PF > lipase CC> PPL. These enzymes were also active for the polymerization of other macrolides. NMR analysis showed that the terminal structure of the polymer was of carboxylic acid at one end and of alcohol at the other terminal. 

Ward et al. [125] investigated the disposition of 14C-radiolabeled primaquine in the isolated perfused rat liver preparation, after the administration of 0.5, 1.5, and 5 mg doses of the drug. The pharmacokinetics of primaquine in the experimental model was dependent on dose size. Increasing the dose from 0.5 to 5 mg produced a significant reduction in clearance from 11.6 to 2.9 mL/min. This decrease was accompanied by a disproportionate increase in the value of the area under the curve from 25.4 to 1128.6 pg/mL, elimination half-life from 33.2 to 413 min, and volume of distribution from 547.7 to 1489 mL. Primaquine exhibited dose dependency in its pattern of metabolism. While the carboxylic acid derivative of primaquine was not detected perfusate after the 0.5 mg dose, it was the principal perfusate metabolite after 5 mg dose. Primaquine was subject to extensive biliary excretion at all doses, the total amount of 14C-radioactivity excreted in the bile decreased from 60 to 30%i as the dose of primaquine was increased from 0.5 to 5 mg. 

Mihaly et al. [127] examined the pharmacokinetics of primaquine in healthy volunteers who received single oral doses of 15, 30, and 45 mg of the drug, on separate occasions. Each subject received an intravenous tracer dose of 14C-prima-quine (7.5 pCi), simultaneously with 45 mg oral dose. Absorption of primaquine was virtually complete with a mean absorption bioavailability of 0.96. Elimination half-life, oral clearance, and apparent volume of distribution for both primaquine and the carboxylic acid metabolite were unaffected by either dose size or route of administration. 

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